Infection with high-risk (HR) human papillomaviruses (HPVs), especially HPV 16, is considered a necessary step in the genesis of cervical intraepithelial neoplasia (CIN), a group of precursor lesions for cervical cancer (CC). Our recent data demonstrated that women with higher folate status have the ability to clear HR-HPV infections, including HPV 16, and that HR-HPV positive women, especially HPV 16-positive women who have lower folate status, are significantly more likely to be diagnosed with CIN (OR=9, p <0.0001). If supplementation with folic acid can enhance the clearance of HPV 1.6 and decrease the incidence of CIN, it would represent a clinically significant intervention. We propose to investigate the effect of supplementation with folic acid on the clearance of HPV 16 and of any of 17 other specific types of HPVs, and on the incidence of CIN, by conducting a 12-month double-blind, placebo-controlled trial of supplementation with 5 mg of folic acid per day. Primary hypotheses: 1) The proportion of women who clear a given specific type of HPV (HPV 16 and any other type present) during the 12 month study period will be higher among those supplemented with 5 mg of folic acid than among those given a placebo. 2) Incidence of CIN will be lower among those supplemented with 5 mg of folic acid than among those given a placebo. Secondary hypothesis: Lower levels of circulating and/or cervical cell folate, the presence of micronuclei, global DNA hypomethylation, integrated HPV 16, or a high viral load of HPV 16 in cervical cells at enrollment will reduce the effectiveness of folic acid supplementation on HPV clearance and on prevention of the progression of cervical lesions (less than CIN 1) to CIN 2 or 3. This will be the first intervention trial designed to evaluate folate's effects on specific types of HR-HPV, its protective role in HR- HPV associated incidence of CIN, and the mechanisms of action of folate on the behavior of HR-HPV. It will aid greatly in understanding the mechanisms of action of folate in cervical carcinogenesis. Public information: Infection with certain types of human papillomaviruses (HPVs), which are sexually transmitted, is considered a necessary step in the genesis of cervical intraepithelial neoplasia (CIN), precursor lesions for cervical cancer (CC). Control of these infections would offer a cost-effective long-term strategy to reduce the CC burden. Our recently completed studies strongly suggest that supplementation with a safe vitamin (folic acid) may reduce the HPV associated risk of CC. Because this study will be conducted among women positive for HPV 16, the most prevalent and powerful causative agent of CC, the public health significance of this study could be enormous and will complement HPV vaccine studies. [unreadable] [unreadable] [unreadable]